Urinary albumin-to-creatinine ratio within normal range and all-cause or cardiovascular mortality among U.S. adults enrolled in the NHANES during 1999–2015

Purpose: Urinary albumin-to-creatinine ratio (UACR) is one of the important diagnostic markers of chronic kidney disease. We aimed to investigate the association between UACR within normal range and cardiovascular or all-cause mortality. Methods: This study included a nationally representative sample of 31,413 U.S. adults aged greater than or equal to 20 years enrolled in the National Health and Nutrition Examination Survey 1999–2014. Mortality was ascertained through 2015. We used multivariable Cox proportional models to investigate the association of UACR with all-cause and cardiovascular mortality. Stratum-specific analyses were conducted by age, sex, race, education status, and comorbidities (e.g., hypertension, diabetes, cardiovascular disease, and chronic kidney disease). Results: Over a median follow-up of 7.6 years, 2854 all-cause deaths and 454 cardiovascular deaths were identified. Higher UACR (per 10 mg/g) was associated with increased risk of all-cause mortality (adjusted hazard ratio = 1.29, 95% confidence interval = 1.22–1.37) and cardiovascular mortality (adjusted hazard ratio = 1.34, 95% confidence interval = 1.17–1.55). The association was larger among women for both all-cause and cardiovascular mortality, and among younger and highly educated participants only for all-cause mortality. The association did not differ by the presence of comorbidities. Conclusions: Elevated UACR within normal range was associated with higher all-cause and cardiovascular mortality risk across almost all subgroups including participants without comorbidities. Our findings suggest the importance of the early detection of albuminuria and careful evaluation of UACR even within normal range to reduce mortality risk.